TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection

The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed...
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Autor*in:	Mustafa Akkoyunlu [verfasserIn] Kadriye Uslu Masahide Yano Adam S. Coleman Shafiuddin Siddiqui Kazuyo Takeda Parna Bhattacharya Hira L. Nakhasi Windy R. Allman Lunhua Liu Ranadhir Dey

Format:	Artikel
Sprache:	Englisch

Erschienen:	2015

Rechteinformationen:	Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences

Schlagwörter:	Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction

Übergeordnetes Werk:	Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 112(2015), 30, Seite E4094
Übergeordnetes Werk:	volume:112 ; year:2015 ; number:30 ; pages:E4094

Links:	Volltext Link aufrufen Link aufrufen Link aufrufen

DOI / URN:	10.1073/pnas.1421580112

Katalog-ID:	OLC197027896X

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520			\|a The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated.
540			\|a Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences
650		4	\|a Macrophages - metabolism
650		4	\|a Leishmania - pathogenicity
650		4	\|a Antigens, CD14 - metabolism
650		4	\|a B-Cell Activating Factor - metabolism
650		4	\|a Macrophages - immunology
650		4	\|a Transmembrane Activator and CAML Interactor Protein - metabolism
650		4	\|a Leishmaniasis - immunology
650		4	\|a Transmembrane Activator and CAML Interactor Protein - genetics
650		4	\|a Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism
650		4	\|a Leishmaniasis - metabolism
650		4	\|a Host-bacteria relationships
650		4	\|a Leishmaniasis
650		4	\|a Phenotype
650		4	\|a Macrophages
650		4	\|a Disease susceptibility
650		4	\|a Health aspects
650		4	\|a Observations
650		4	\|a Genetic aspects
650		4	\|a Gene expression
650		4	\|a Genotype & phenotype
650		4	\|a Protozoa
650		4	\|a Cells
650		4	\|a Signal transduction
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700	0		\|a Parna Bhattacharya \|4 oth
700	0		\|a Hira L. Nakhasi \|4 oth
700	0		\|a Windy R. Allman \|4 oth
700	0		\|a Lunhua Liu \|4 oth
700	0		\|a Ranadhir Dey \|4 oth
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773	1	8	\|g volume:112 \|g year:2015 \|g number:30 \|g pages:E4094
856	4	1	\|u http://dx.doi.org/10.1073/pnas.1421580112 \|3 Volltext
856	4	2	\|u http://www.pnas.org/content/112/30/E4094.abstract
856	4	2	\|u http://www.ncbi.nlm.nih.gov/pubmed/26170307
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allfields	10.1073/pnas.1421580112 doi PQ20160211 (DE-627)OLC197027896X (DE-599)GBVOLC197027896X (PRQ)g1827-8874ee62838cb388469429de7d880e0102cda8e07aa767f485c72cc005e798690 (KEY)0583363920150000112003004094tacideficiencyleadstoalternativelyactivatedmacroph DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Mustafa Akkoyunlu verfasserin aut TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction Kadriye Uslu oth Masahide Yano oth Adam S. Coleman oth Shafiuddin Siddiqui oth Kazuyo Takeda oth Parna Bhattacharya oth Hira L. Nakhasi oth Windy R. Allman oth Lunhua Liu oth Ranadhir Dey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 30, Seite E4094 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:30 pages:E4094 http://dx.doi.org/10.1073/pnas.1421580112 Volltext http://www.pnas.org/content/112/30/E4094.abstract http://www.ncbi.nlm.nih.gov/pubmed/26170307 http://search.proquest.com/docview/1701281649 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 30 E4094
spelling	10.1073/pnas.1421580112 doi PQ20160211 (DE-627)OLC197027896X (DE-599)GBVOLC197027896X (PRQ)g1827-8874ee62838cb388469429de7d880e0102cda8e07aa767f485c72cc005e798690 (KEY)0583363920150000112003004094tacideficiencyleadstoalternativelyactivatedmacroph DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Mustafa Akkoyunlu verfasserin aut TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction Kadriye Uslu oth Masahide Yano oth Adam S. Coleman oth Shafiuddin Siddiqui oth Kazuyo Takeda oth Parna Bhattacharya oth Hira L. Nakhasi oth Windy R. Allman oth Lunhua Liu oth Ranadhir Dey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 30, Seite E4094 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:30 pages:E4094 http://dx.doi.org/10.1073/pnas.1421580112 Volltext http://www.pnas.org/content/112/30/E4094.abstract http://www.ncbi.nlm.nih.gov/pubmed/26170307 http://search.proquest.com/docview/1701281649 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 30 E4094
allfields_unstemmed	10.1073/pnas.1421580112 doi PQ20160211 (DE-627)OLC197027896X (DE-599)GBVOLC197027896X (PRQ)g1827-8874ee62838cb388469429de7d880e0102cda8e07aa767f485c72cc005e798690 (KEY)0583363920150000112003004094tacideficiencyleadstoalternativelyactivatedmacroph DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Mustafa Akkoyunlu verfasserin aut TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction Kadriye Uslu oth Masahide Yano oth Adam S. Coleman oth Shafiuddin Siddiqui oth Kazuyo Takeda oth Parna Bhattacharya oth Hira L. Nakhasi oth Windy R. Allman oth Lunhua Liu oth Ranadhir Dey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 30, Seite E4094 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:30 pages:E4094 http://dx.doi.org/10.1073/pnas.1421580112 Volltext http://www.pnas.org/content/112/30/E4094.abstract http://www.ncbi.nlm.nih.gov/pubmed/26170307 http://search.proquest.com/docview/1701281649 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 30 E4094
allfieldsGer	10.1073/pnas.1421580112 doi PQ20160211 (DE-627)OLC197027896X (DE-599)GBVOLC197027896X (PRQ)g1827-8874ee62838cb388469429de7d880e0102cda8e07aa767f485c72cc005e798690 (KEY)0583363920150000112003004094tacideficiencyleadstoalternativelyactivatedmacroph DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Mustafa Akkoyunlu verfasserin aut TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction Kadriye Uslu oth Masahide Yano oth Adam S. Coleman oth Shafiuddin Siddiqui oth Kazuyo Takeda oth Parna Bhattacharya oth Hira L. Nakhasi oth Windy R. Allman oth Lunhua Liu oth Ranadhir Dey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 30, Seite E4094 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:30 pages:E4094 http://dx.doi.org/10.1073/pnas.1421580112 Volltext http://www.pnas.org/content/112/30/E4094.abstract http://www.ncbi.nlm.nih.gov/pubmed/26170307 http://search.proquest.com/docview/1701281649 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 30 E4094
allfieldsSound	10.1073/pnas.1421580112 doi PQ20160211 (DE-627)OLC197027896X (DE-599)GBVOLC197027896X (PRQ)g1827-8874ee62838cb388469429de7d880e0102cda8e07aa767f485c72cc005e798690 (KEY)0583363920150000112003004094tacideficiencyleadstoalternativelyactivatedmacroph DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Mustafa Akkoyunlu verfasserin aut TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection 2015 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction Kadriye Uslu oth Masahide Yano oth Adam S. Coleman oth Shafiuddin Siddiqui oth Kazuyo Takeda oth Parna Bhattacharya oth Hira L. Nakhasi oth Windy R. Allman oth Lunhua Liu oth Ranadhir Dey oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 112(2015), 30, Seite E4094 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:112 year:2015 number:30 pages:E4094 http://dx.doi.org/10.1073/pnas.1421580112 Volltext http://www.pnas.org/content/112/30/E4094.abstract http://www.ncbi.nlm.nih.gov/pubmed/26170307 http://search.proquest.com/docview/1701281649 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 112 2015 30 E4094
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author	Mustafa Akkoyunlu
spellingShingle	Mustafa Akkoyunlu ddc 500 ddc 570 fid LING fid BIODIV misc Macrophages - metabolism misc Leishmania - pathogenicity misc Antigens, CD14 - metabolism misc B-Cell Activating Factor - metabolism misc Macrophages - immunology misc Transmembrane Activator and CAML Interactor Protein - metabolism misc Leishmaniasis - immunology misc Transmembrane Activator and CAML Interactor Protein - genetics misc Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism misc Leishmaniasis - metabolism misc Host-bacteria relationships misc Leishmaniasis misc Phenotype misc Macrophages misc Disease susceptibility misc Health aspects misc Observations misc Genetic aspects misc Gene expression misc Genotype & phenotype misc Protozoa misc Cells misc Signal transduction TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection
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topic_title	500 DNB 570 AVZ LING fid BIODIV fid TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection Macrophages - metabolism Leishmania - pathogenicity Antigens, CD14 - metabolism B-Cell Activating Factor - metabolism Macrophages - immunology Transmembrane Activator and CAML Interactor Protein - metabolism Leishmaniasis - immunology Transmembrane Activator and CAML Interactor Protein - genetics Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism Leishmaniasis - metabolism Host-bacteria relationships Leishmaniasis Phenotype Macrophages Disease susceptibility Health aspects Observations Genetic aspects Gene expression Genotype & phenotype Protozoa Cells Signal transduction
topic	ddc 500 ddc 570 fid LING fid BIODIV misc Macrophages - metabolism misc Leishmania - pathogenicity misc Antigens, CD14 - metabolism misc B-Cell Activating Factor - metabolism misc Macrophages - immunology misc Transmembrane Activator and CAML Interactor Protein - metabolism misc Leishmaniasis - immunology misc Transmembrane Activator and CAML Interactor Protein - genetics misc Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism misc Leishmaniasis - metabolism misc Host-bacteria relationships misc Leishmaniasis misc Phenotype misc Macrophages misc Disease susceptibility misc Health aspects misc Observations misc Genetic aspects misc Gene expression misc Genotype & phenotype misc Protozoa misc Cells misc Signal transduction
topic_unstemmed	ddc 500 ddc 570 fid LING fid BIODIV misc Macrophages - metabolism misc Leishmania - pathogenicity misc Antigens, CD14 - metabolism misc B-Cell Activating Factor - metabolism misc Macrophages - immunology misc Transmembrane Activator and CAML Interactor Protein - metabolism misc Leishmaniasis - immunology misc Transmembrane Activator and CAML Interactor Protein - genetics misc Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism misc Leishmaniasis - metabolism misc Host-bacteria relationships misc Leishmaniasis misc Phenotype misc Macrophages misc Disease susceptibility misc Health aspects misc Observations misc Genetic aspects misc Gene expression misc Genotype & phenotype misc Protozoa misc Cells misc Signal transduction
topic_browse	ddc 500 ddc 570 fid LING fid BIODIV misc Macrophages - metabolism misc Leishmania - pathogenicity misc Antigens, CD14 - metabolism misc B-Cell Activating Factor - metabolism misc Macrophages - immunology misc Transmembrane Activator and CAML Interactor Protein - metabolism misc Leishmaniasis - immunology misc Transmembrane Activator and CAML Interactor Protein - genetics misc Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism misc Leishmaniasis - metabolism misc Host-bacteria relationships misc Leishmaniasis misc Phenotype misc Macrophages misc Disease susceptibility misc Health aspects misc Observations misc Genetic aspects misc Gene expression misc Genotype & phenotype misc Protozoa misc Cells misc Signal transduction
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title	TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection
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title_full	TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection
author_sort	Mustafa Akkoyunlu
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title_sort	taci deficiency leads to alternatively activated macrophage phenotype and susceptibility to leishmania infection
title_auth	TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection
abstract	The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated.
abstractGer	The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated.
abstract_unstemmed	The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated.
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title_short	TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection
url	http://dx.doi.org/10.1073/pnas.1421580112 http://www.pnas.org/content/112/30/E4094.abstract http://www.ncbi.nlm.nih.gov/pubmed/26170307 http://search.proquest.com/docview/1701281649
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up_date	2024-07-03T14:36:56.931Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC197027896X</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230714175939.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">160211s2015 xx \|\|\|\|\| 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1073/pnas.1421580112</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20160211</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC197027896X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC197027896X</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)g1827-8874ee62838cb388469429de7d880e0102cda8e07aa767f485c72cc005e798690</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0583363920150000112003004094tacideficiencyleadstoalternativelyactivatedmacroph</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">500</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">570</subfield><subfield code="q">AVZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">LING</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">BIODIV</subfield><subfield code="2">fid</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Mustafa Akkoyunlu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2015</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated.</subfield></datafield><datafield tag="540" ind1=" " ind2=" "><subfield code="a">Nutzungsrecht: © COPYRIGHT 2015 National Academy of Sciences</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Macrophages - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Leishmania - pathogenicity</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Antigens, CD14 - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">B-Cell Activating Factor - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Macrophages - immunology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Transmembrane Activator and CAML Interactor Protein - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Leishmaniasis - immunology</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Transmembrane Activator and CAML Interactor Protein - genetics</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Leishmaniasis - metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Host-bacteria relationships</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Leishmaniasis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Phenotype</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Macrophages</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Disease susceptibility</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Health aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Observations</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genetic aspects</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gene expression</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Genotype & phenotype</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Protozoa</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Cells</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Signal transduction</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Kadriye Uslu</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Masahide Yano</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Adam S. 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TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection

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